Development of safe and effective agents for reducing the risk of cancer and other chronic diseases is a high priority of contemporary medicine. Implementation of strategies for chemoprevention/chemoprotection is beset with many problems.
In the economically developed world, the mammary gland is the most common target of malignancy in women. Thus, in the U.S. alone, 232,340 new diagnoses and 39,620 deaths of women from breast cancer were projected for 2013, and the global burden of new cases is enormous. The majority of breast malignancies are estrogen receptor-positive at the time of diagnosis and their growth is under estrogen control: thus this process is an effective target for both prevention and treatment of breast cancer by two mechanisms: (i) selective modification of estrogen binding to their receptors exemplified by such widely used agents as tamoxifen and raloxifene, and (ii) blocking of estrogen biosynthesis by inhibition of its final and rate-limiting step, the aromatase reaction, by steroidal compounds such as exemestane and nonsteroidal letrozole and anastrozole. Both these approaches have been highly successful, and multiple clinical studies attest to their benefits. Thus, a recent study of 4560 women at moderately increased risk for developing breast cancer showed that exemestane reduced the risk of breast cancer by 65% relative to placebo. Exemestane has been administered to women with breast cancer in combination with tamoxifen or with cyclooxygenase inhibitors, without increased adverse effects.
Albeit exemestrane has been tested in males, it is considered generally as an aromatase inhibitor. Mauras, N. et al., J. Clin. Endocrin. Metab. 88(12):5951-5956 (2003).